Submissions for variant NM_001394062.1(MACF1):c.20743G>A (p.Glu6915Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003448803	SCV004176541	uncertain significance	Lissencephaly 9 with complex brainstem malformation	2023-02-14	criteria provided, single submitter	clinical testing	The missense c.14566G>A(p.Glu4856Lys) variant in MACF1 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Glu4856Lys variant is novel (not in any individuals) in both gnomAD Exomes and 1000 Genomes databases. This variant has not been reported to the ClinVar database. The amino acid change p.Glu4856Lys in MACF1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Glu at position 4856 is changed to a Lys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).
GeneDx	RCV005230510	SCV005875224	uncertain significance	not provided	2024-08-26	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge